title: Glucagon-like peptide-1 suppresses advanced glycation end product-induced monocyte chemoattractant protein-1 expression in mesangial cells by reducing advanced glycation end product receptor level.
abstract: Advanced glycation end products (AGE) and receptor for AGE (RAGE) interaction elicits reactive oxygen species (ROS) generation and inflammatory reactions, thereby being involved in the development and progression of diabetic nephropathy. Recently, we, along with others, found that glucagon-like peptide-1 (GLP-1), one of the incretins and a gut hormone secreted from L cells in the intestine in response to food intake, could have anti-inflammatory and antithrombogenic properties in cultured endothelial cells. However, the effects of GLP-1 on renal mesangial cells are largely unknown. Therefore, to elucidate the role of GLP-1 in diabetic nephropathy, this study investigated whether and how GLP-1 blocked AGE-induced monocyte chemoattractant protein-1 expression in human cultured mesangial cells. Gene and protein expression was analyzed by quantitative real-time reverse transcription polymerase chain reactions, Western blots, and enzyme-linked immunosorbent assay. The ROS generation was measured with dihydroethidium staining. Glucagon-like peptide-1 receptor (GLP-1R) was expressed in mesangial cells. Glucagon-like peptide-1 inhibited RAGE gene expression in mesangial cells, which was blocked by small interfering RNAs raised against GLP-1R. Furthermore, GLP-1 decreased ROS generation and subsequently reduced monocyte chemoattractant protein-1 gene and protein expression in AGE-exposed mesangial cells. An analogue of cyclic adenosine monophosphate mimicked the effects of GLP-1 on mesangial cells. Our present study suggests that GLP-1 may directly act on mesangial cells via GLP-1R and that it could work as an anti-inflammatory agent against AGE by reducing RAGE expression via activation of cyclic adenosine monophosphate pathway.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nishino
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D018027:Receptors, Glucagon / Q000032:analysis / Q000502:physiology; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D018027:Receptors, Glucagon; D011971:Receptors, Immunologic; D052216:Glucagon-Like Peptide 1